This invention relates to pharmaceutical compositions comprising an agent that binds to α-2,3-sialic acid transmembrane glycoproteins and methods of using these pharmaceutical compositions for treating joint inflammatory disease, as well as methods for preventing the degradation of cartilage.
Joint inflammatory disease can be characterized as inflammation of the joint that may cause pain, stiffness, and some redness of the skin about the joint, and can be a result of an infection, physical injury, autoimmune disease or a type of arthritis. Effusion of fluid into the joint cavity is common, and examination of this fluid is often a valuable procedure for determining the nature of the disease. The inflammation may be of such a nature and of such severity as to destroy the joint cartilage and underlying bone and cause irreparable deformities. Adhesions between the articulating members are frequent in such cases, and the resulting fusion with loss of mobility is called ankylosis. Inflammation restricted to the lining of a joint (the synovial membrane) is referred to as synovitis. Rheumatoid arthritis (RA) is an autoimmune disease that results in a chronic, systemic inflammatory disorder that principally attacks flexible (synovial) joints. Experimental data suggest that cases of arthritis can exhibit a notable increase in levels of reactive oxygen species (ROS) and proinflammatory cytokines. This process is likely to be pronounced during periods of arthritic flares, and triggers a characteristic degradation of cartilage matrix.
Arthritis is characterized by degradation of the chondrocyte extracellular matrix (ECM), which results in articular cartilage erosion. Susceptibility of articular cartilage to arthritic degradation is associated with posttranslational modifications of ECM proteins. Glycosylation is the most common posttranslational modification of cell surface and ECM proteins. As a result, chondrocytes carry a dense coat of carbohydrates on their surfaces. These carbohydrate moieties mediate a wide variety of cell-cell and cell-matrix interactions that are critical for bone development and function. Current treatments for Arthritis consist mostly of anti-inflammatory and immunosuppressant medications. Unfortunately, these approaches are only modestly effective to ameliorate symptoms, and may cause significant side effects including increased risk of viral infection and cancer. Therefore there is a need for new pharmaceutical compositions and methods to treat arthritis.